Variant 1-26190830-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_198137.2(CATSPER4):c.203C>T(p.Thr68Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,608,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

CATSPER4
NM_198137.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.73

Variant links:

Genes affected

CATSPER4 (HGNC:23220): (cation channel sperm associated 4) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

CATSPER4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029586285).

BP6

Variant 1-26190830-C-T is Benign according to our data. Variant chr1-26190830-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3263541.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CATSPER4	NM_198137.2 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant	1/10	ENST00000456354.7	NP_937770.1
CATSPER4	XM_011541432.4 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant	1/9		XP_011539734.1
CATSPER4	XM_011541433.3 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant	1/7		XP_011539735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CATSPER4	ENST00000456354.7 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant	1/10	1	NM_198137.2	ENSP00000390423	P1	Q7RTX7-1
CATSPER4	ENST00000518899.5 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant, NMD_transcript_variant	1/10	1		ENSP00000429464		Q7RTX7-2
CATSPER4	ENST00000338855.6 linkuse as main transcript	c.203C>T	p.Thr68Met	missense_variant	1/9	5		ENSP00000341006

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000660

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000457

AC:

AN:

240836

Hom.:

AF XY:

0.0000384

AC XY:

AN XY:

130254

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.000194

Gnomad NFE exome

AF:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000158

AC:

AN:

1456912

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724234

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000455

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000820

Gnomad4 FIN exome

AF:

0.000151

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000658

AC:

AN:

152054

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000660

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 29, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.39

CADD

Benign

0.035

DANN

Benign

0.61

DEOGEN2

Benign

0.022

.;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0034

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.030

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

-0.20

.;N

MutationTaster

Benign

1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.36

N;N

REVEL

Benign

0.26

Sift

Benign

0.59

T;T

Sift4G

Benign

0.67

T;T

Polyphen

0.0050

.;B

Vest4

0.089

MVP

0.33

MPC

0.18

ClinPred

0.018

GERP RS

-2.4

Varity_R

0.013

gMVP

0.32

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over